Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disease. In humans, AD becomes symptomatic only after brain changes occur over years or decades. Three contiguous phases of AD have been proposed: (i) the AD pathophysiologic process, (ii) mild cognitive impairment due to AD, and (iii) AD dementia. Intensive research continues around the world on unique diagnostic markers and interventions associated with each phase of AD. In this review, we summarize the available evidence and new therapeutic approaches that target both amyloid and tau pathology in AD and discuss the biomarkers and pharmaceutical interventions available and in development for each AD phase.

In this review the existing evidence on the impact of Rashtriya Swasthya Bima Yojana (RSBY) is discussed in the context of international literature available on health insurance. We describe potential pathways through which health insurance can affect health and economic outcomes, discuss evidence from other developing countries, and identify potential biases and inconsistencies in existing studies on RSBY impact. Given the relatively recent introduction of RSBY, lack of quality, verifiable data on utilization patterns, and the absence of reliable evaluation studies, there is a need to exercise caution while assessing the merits of the programme. Considering the enormous potential and cost of the programme, we emphasize the need for a rigorous impact evaluation of RSBY. It will not only help capture the real impact of the scheme, but may also be able to estimate the extent of systemic inefficiencies at the level of the consumer.

Background & objectives: Cancer stem cells (CSCs) may be responsible for tumour recurrence and resistance to chemotherapy in hepatocellular carcinoma (HCC). This study was carried out to evaluate the association between histological parameters and liver CSCs (LCSC) in HCC, and to compare distribution of liver CSCs in HCC associated with and without hepatitis B virus (HBV) infection.
Methods: Seventy nine tumours (49 surgical resections from 46 patients, and 30 from autopsy) were reviewed. Immunohistochemical staining for the LCSC marker EpCAM (epithelial cell adhesion molecule), liver progenitor cell (LPC) markers CK19 (cytokeratin 19) and neural cell adhesion molecule (NCAM) were performed and were associated with histological features of tumour behaviour.
Results: Thirty three tumours (41.8%) showed positive staining for EpCAM. CK19 and NCAM expression were seen in 26 (32.9%) and four (5.1%) tumours, respectively. The expression of EpCAM and CK19 was significantly associated with each other ( P<0.001). EpCAM expression was significantly associated with clinical and histological features indicating aggressive tumour behaviour, including younger age of onset, higher serum alpha foetoprotein (AFP) levels, tumour cell dedifferentiation, increased mitotic activity, and vascular invasiveness. There was no significant difference in expression of EpCAM, CK19 and NCAM between HBV positive and negative HCC.
Interpretation & conclusions:The LCSC marker EpCAM was expressed in less than half of HCC, was independent of HBV aetiology, and was strongly associated with clinical and histological features of aggressive tumour behaviour. Positive staining for CK19 suggests a possible LPC origin of the EpCAM positive HCCs.

Background & objectives: Patients frequently experience pain of moderate to severe degree during gynaecologic procedures. This prospective, randomized, placebo-controlled trial was aimed to investigate the analgesic efficacy of preoperative oral dexketoprofen trometamol, intravenous paracetamol, lidocaine spray, pethidine and diclofenac sodium on fractional curettage procedure.
Methods: A total of 144 mutiparous women were randomly allocated to one of the six groups. The first group (control group) consisted of 22 participants and they did not receive any treatment. The second group had 26 participants receiving oral 25 mg dexketoprofen trometamol. The 23 participants of the third group received two puff lidocaine sprays on cervical mucosa. t0 he forth group consisted of 25 participants receiving 100 mg pethidine. In the fifth group, the 23 participants received 1000 mg intravenous paracetamol and the sixth group consisted of 25 participants receiving diclofenac sodium.
Results: Pethidine was the best choice for reducing pain score during curettage procedure (t2:intra-operative). All analgesic procedures were significantly effective in reducing pain during postoperative period (t3). Significant pain reduction was achieved for both intra- and postoperative period by using analgesics.
Interpretation & conclusions: The results of our study showed that lidocaine puffs provided the best pain relief than the other analgesics used. Therefore, lidocaine may be considered as the first choice analgesic in fractional curettage (NCT ID: 01993589).

Background & objectives: CD4 + T cells are involved in abnormal inflammatory responses causing adverse effects to the body. Th17 cells play a major role in immune disorders and the exact mechanism by which CD4 + T cells regulate its effector Th1 and Th17 phenotype at chromatin level is not clearly understood. This study was aimed to understand the role of matrix associated region (MAR) binding protein SMAR1 (scaffold/matrix attachment region binding protein 1) in T cell differentiation during inflammatory and autoimmune condition using SMAR1 transgenic mice as model.
Methods: Wild type (C57BL/6J) and SMAR1 transgenic mice were used for isolation of T cells and further identification of different T cell lineages, along with histological analysis. Further, we studied autoimmune and inflammatory diseases using chemically induced and T cell transfer model of colitis and rheumatoid arthritis to better understand the role of SMAR1 in immune responses.
Results: SMAR1 transgenic mice were resistant to dextran sodium sulphate (DSS) induced colitis with decreased expression of Th1 and Th17 specific cytokines. Overexpression of SMAR1 repressed Th17 response by negatively regulating RORγt and IL-17 expression. Downregulation of SMAR1 upregulated signal transducer and activator of transcription 3 (pSTAT3) and IL-17 expression that caused generation of more proinflammatory Th1 and Th17 cells leading to inflammation and disease.
Interpretation & conclusions: Our results show an important role of SMAR1 in regulating CD4 + T cell differentiation during inflammatory disorders via regulation of both Th1 and Th17 signaling pathways. This study reveals a critical role of SMAR1 in maintaining the proinflammatory immune responses by repressing Th1 and Th17 cell function and it gives the novel insight into immune regulatory mechanisms.

Background & objectives: Mucopolysaccharidosis type VI (MPS VI) is a rare, autosomal recessive lysosomal storage disorder caused by deficient enzymatic activity of N-acetyl galactosamine-4-sulphatase resulting from mutations in the arylsulphatase B (ARSB) gene. The ARSB gene is located on chromosome 5q11-q13 and is composed of eight exons. More than hundred ARSB mutations have been reported so far, but the mutation spectrum of MPS VI in India is still unknown. Hence, the aim of the present study was to identify the mutational spectrum in patients with MPS VI in India and to study the genotype-phenotype association and functional outcomes of these mutations.
Methods: Molecular characterization of the ARSB gene by Sanger sequencing was done for 15 patients (aged 15 months to 11 yr) who were enzymatically confirmed to have MPS VI. Age of onset, clinical progression and enzyme activity levels in each patient were studied to look for genotype-phenotype association. Haplotype analysis performed for unrelated patients with the recurring mutation W450C, was suggestive of a founder effect. Sequence and structural analyses of the ARSB protein using standard software were carried out to determine the impact of detected mutations on the function of the ARSB protein.
Results: A total of 12 mutations were identified, of which nine were novel mutations namely, p.D53N, p.L98R, p.Y103SfsX9, p.W353X, p.H393R, p.F166fsX18, p.I220fsX5, p.W450L, and p.W450C, and three were known mutations (p.D54N, p.A237D and p.S320R). The nine novel sequence variants were confirmed not to be polymorphic variants by performing sequencing in 50 unaffected individuals from the same ethnic population.
Interpretation & conclusions: Nine novel mutations were identified in MPS VI cases from India in the present study. The study also provides some insights into the genotype-phenotype association in MPS VI.

Background & objectives: Hairy cell leukaemia (HCL) is a B cell neoplasm which constitutes around 2 per cent of all the lymphoid leukaemias. It has a characteristic morphology and immunophenotypic profile. It is important to distinguish HCL from other B cell lymphoproliferative disorders due to availability of different chemotherapeutic agents. This study presents clinical, haematological and immunophenotypic profile of patients with HCL seen over a period of four years in a tertiary care hospital in north India.
Methods: Twenty one cases of hairy cell leukaemia were analyzed for their clinical details, haemogram, bone marrow examination and immunophenotypic findings.
Results: Age of the patients ranged from 28-76 yr with male predominance. Weakness and fever were commonest presentations. Splenomegaly, hepatomegaly, lymphadenopathy were seen in decreasing order of frequency. Anaemia was noted in all 21 patients, leukopenia in 15 and thrombocytopenia in 19 cases. Fourteen patients were pancytopenic. Bone marrow examination showed typical hairy cells in all cases. Immunophenotyping showed expression of CD19, CD20, CD103, CD25 and CD11c in all cases, while positivity was seen for CD79b in 93.7 per cent, kappa light chain restriction in 60 per cent and lambda in 40 per cent cases. Notably, 20 per cent showed CD10 and 12 per cent showed CD23 expression.
Interpretation & conclusions: This study reveals some unusual findings in otherwise classical disease entity, like absence of palpable spleen, presence of lymphadenopathy, normal or elevated leukocyte counts, expression of CD10, which at times could be diagnostically challenging.

Background & objectives: There are only a few reports available on characterization of Propionibacterium acnes isolated from various ocular clinical specimens. We undertook this study to evaluate the role of P. acnes in ocular infections and biofilm production, and also do the phylogenetic analysis of the bacilli.
Methods: One hundred isolates of P. acnes collected prospectively from ocular clinical specimens at a tertiary care eye hospital between January 2010 and December 2011, were studied for their association with various ocular disease conditions. The isolates were also subjected to genotyping and phylogenetic analysis, and were also tested for their ability to produce biofilms.
Results: Among preoperative conjunctival swabs, P.acnes was a probably significant pathogen in one case; a possibly significant pathogen in two cases. In other clinical conditions, 13 per cent isolates were probably significant pathogens and 38 per cent as possibly significant pathogens. The analysis of 16S rRNA gene revealed four different phylogenies whereas analysis of recA gene showed two phylogenies confirming that recA gene was more reliable than 16S rRNA with less sequence variation. Results of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) had 100 per cent concordance with phylogenetic results. No association was seen between P. acnes subtypes and biofilm production.
Interpretation & conclusions:RecA gene phylogenetic studies revealed two different phylogenies. RFLP technique was found to be cost-effective with high sensitivity and specificity in phylogenetic analysis. No association between P. acnes subtypes and pathogenetic ability was observed. Biofilm producing isolates showed increased antibiotic resistance compared with non-biofilm producing isolates.

Background & objectives: Multiple sclerosis (MS) is a neurodegenerative disease, which affects the patients' mobility, and exercise training is considered to be beneficial for these patients. The aim of this study was to determine the effects of 10 wk of low intensity exercise and whole body vibration (WBV) training on fatigue, quality of life, functional and physical indices, and serum levels of ghrelin, leptin, and testosterone in MS patients.
Methods: Thirty four MS patients with mild to moderate disability were recruited and randomly divided into two groups, the training group (n=17) and control group (n=17). Patients in the training group did low intensity exercise and WBV training programme three times a week for 10 wk. The control group continued their routine life. Intended variables like expanded disability status scale (EDSS), fatigue, quality of life, functional and physical indices consisted of balance, walking speed, functional mobility, functional muscle endurance, and walking endurance, and serum levels of ghrelin, leptin, and testosterone were measured before and after the protocol.
Results: Thirty subjects completed the study (23 females, 7 males; mean age =38.80 ± 9.50 yr). Statistical analysis demonstrated that EDSS in the WBV training group was significantly decreased (P=0.01), balance (P=0.01), and walking endurance significantly increased (P=0.01) in MS patients (P<0.05).
Interpretation & conclusions: The results suggest that low intensity exercise and WBV training have some beneficial impact on functional and physical indices of MS patients.

Despite the introduction of mass immunization, diphtheria continues to play a major role as a potentially lethal infectious disease in many countries. Delay in the specific therapy of diphtheria may result in death and, therefore, accurate diagnosis of diphtheria is imperative. This study was carried out at National Centre for Disease Control (NCDC), Delhi, India, on samples of suspected diphtheria cases referred from various government hospitals of Delhi and neighbouring areas during 2012-2014. Primary identification of Corynebacterium diphtheriae was done by standard culture, staining and biochemical tests followed by toxigenicity testing by Elek's test on samples positive for C. diphtheriae. The results showed persistence of toxigenic C. diphtheriae in our community indicating the possibility of inadequate immunization coverage.

Background & objectives: Dietary fibre-rich tender cluster beans (Cyamopsis tetragonoloba; CB) are known to exert beneficial cholesterol lowering influence. We examined the influence of a combination of dietary tender CB and garlic (Allium sativum) in reducing the cholesterol gallstone formation in mice.
Methods: Cholesterol gallstones were induced in Swiss mice by feeding a high-cholesterol diet (HCD) for 10 wk. Dietary interventions were made with 10 per cent CB and 1 per cent garlic included individually or together along with HCD. A total of 100 mice were divided into five groups of 20 mice each.
Results: Dietary CB, garlic and CB+garlic reduced the formation of cholesterol gallstones by 44, 25 and 56 per cent, respectively, lowered cholesterol by 23-48, 16-24, and 24-58 in bile, serum, and liver, respectively. Cholesterol saturation index in bile and cholesterol: phospholipid ratio in circulation and hepatic tissue were significantly lowered by these dietary interventions, with highest beneficial effect from CB+garlic. Activities of hepatic cholesterol metabolizing enzymes were modulated by CB, garlic and CB+garlic. Elevation in lipid peroxides caused by HCD was also countered by these dietary interventions, the combination producing the highest effect.
Interpretation & conclusions:The results showed that the prevention of experimentally induced formation of cholesterol gallstones by dietary CB and garlic was due to decreased biliary cholesterol secretion and increased cholesterol saturation index. In addition of anti-lithogenic effect, dietary CB and garlic in combination had a beneficial antioxidant effect.

Background & objectives: The poliovirus serotype identification and intratypic differentiation by real-time reverse transcription-polymerase chain reaction (rRT-PCR) assay is suitable for serotype mixtures but not for intratypic mixtures of wild and vaccine poliovirus strains. This study was undertaken to develop wild poliovirus 1 and 3 (WPV1 and WPV3) specific rRT-PCR assays for use.
Methods: Specific primers and probes for rRT-PCR were designed based on VP1 sequences of WPV1 and WPV3 isolated in India since 2000. The specificity of the rRT-PCR assays was evaluated using WPV1 and WPV3 of different genetic lineages, non-polio enteroviruses (NPEVs) and mixtures of wild/wild and wild/Sabin vaccine strains. The sensitivity of the assays was determined by testing serial 10-fold dilutions of wild poliovirus 1 and 3 stock suspensions of known titre.
Results: No cross-reactivity with Sabin strains, intertypic wild poliovirus isolates or 27 types of NPEVs across all the four Enterovirus species was found for both the wild poliovirus 1 and 3 rRT-PCR assays. All WPV1 and WPV3 strains isolated since 2000 were successfully amplified. The rRT-PCR assays detected 10 4.40 CCID 50 /ml of WPV1 and 10 4.00 CCID 50 /ml of WPV3, respectively either as single isolate or mixture with Sabin vaccine strains or intertypic wild poliovirus.
Interpretation & conclusions: rRT-PCR assays for WPV1 and WPV3 have been validated to detect all the genetic variations of the WPV1 and WPV3 isolated in India for the last decade. When used in combination with the current rRT-PCR assay testing was complete for confirmation of the presence of wild poliovirus in intratypic mixtures.

Background & objectives: In India, community based data on chronic obstetric morbidities (COM) are scanty and largely derived from hospital records. The main aim of the study was to assess the community based prevalence and the factors associated with the defined COM - obstetric fistula, genital prolapse, chronic pelvic inflammatory disease (PID) and secondary infertility among women in Nashik district of Maharashtra State, India.
Methods: The study was cross-sectional with self-reports followed by clinical and gynaecological examination. Six primary health centre areas in Nashik district were selected by systematic random sampling. Six months were spent on rapport development with the community following which household interviews were conducted among 1560 women and they were mobilized to attend health facility for clinical examination.
Results: o0 f the 1560 women interviewed at household level, 1167 women volunteered to undergo clinical examination giving a response rate of 75 per cent. The prevalence of defined COM among 1167 women was genital prolapse (7.1%), chronic PID (2.5%), secondary infertility (1.7%) and fistula (0.08%). Advancing age, illiteracy, high parity, conduction of deliveries by traditional birth attendants (TBAs) and obesity were significantly associated with the occurrence of genital prolapse. History of at least one abortion was significantly associated with secondary infertility. Chronic PID had no significant association with any of the socio-demographic or obstetric factors.
Interpretation & conclusions: The study findings provided an insight in the magnitude of community-based prevalence of COM and the factors associated with it. The results showed that COM were prevalent among women which could be addressed by interventions at personal, social and health services delivery level.